State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer
Two-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/3470 |
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| author | Horatiu Silaghi Vera Lozovanu Carmen Emanuela Georgescu Cristina Pop Bogdana Adriana Nasui Adriana Florinela Cătoi Cristina Alina Silaghi |
| author_facet | Horatiu Silaghi Vera Lozovanu Carmen Emanuela Georgescu Cristina Pop Bogdana Adriana Nasui Adriana Florinela Cătoi Cristina Alina Silaghi |
| author_sort | Horatiu Silaghi |
| collection | DOAJ |
| description | Two-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting specific genetic dysregulations. Lenvatinib and sorafenib are first-line, multitargeted tyrosine kinase inhibitors (TKIs) approved to treat advanced, progressive RAIR-DTC. However, other anti-angiogenic drugs, including single targeted TKIs, are currently being evaluated as alternative or salvage therapy after the failure of first-line TKIs. Combinatorial therapy of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling cascade inhibitors has become a highly advocated strategy to improve the low efficiency of the single agent treatment. Recent studies pointed out targetable alternative pathways to overcome the resistance to MAPK and PI3K pathways’ inhibitors. Because radioiodine resistance originates in DTC loss of differentiation, redifferentiation therapies are currently being explored for efficacy. The present review will summarize the conventional management of DTC, the first-line and alternative TKIs in RAIR-DTC, and the approaches that seek to overcome the resistance to MAPK and PI3K pathways’ inhibitors. We also aim to emphasize the latest achievements in the research of redifferentiation therapy, immunotherapy, and agents targeting gene rearrangements in advanced DTC. |
| first_indexed | 2024-03-09T11:49:38Z |
| format | Article |
| id | doaj.art-93d91a6eca8747afb223bf1584ee1d26 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:49:38Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-93d91a6eca8747afb223bf1584ee1d262023-11-30T23:17:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237347010.3390/ijms23073470State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid CancerHoratiu Silaghi0Vera Lozovanu1Carmen Emanuela Georgescu2Cristina Pop3Bogdana Adriana Nasui4Adriana Florinela Cătoi5Cristina Alina Silaghi6Department of Surgery V, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaCounty Clinical Emergency Hospital Cluj, 3-5 Clinicilor Street, 400006 Cluj-Napoca, RomaniaDepartment of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaDepartment of Pharmacology, Physiology, and Pathophysiology, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 6A Louis Pasteur Street, 400349 Cluj-Napoca, RomaniaDepartment of Community Health, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 6 Louis Pasteur Street, 400349 Cluj-Napoca, RomaniaDepartment of Pathophysiology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaDepartment of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, 8 Victor Babes Street, 400012 Cluj-Napoca, RomaniaTwo-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting specific genetic dysregulations. Lenvatinib and sorafenib are first-line, multitargeted tyrosine kinase inhibitors (TKIs) approved to treat advanced, progressive RAIR-DTC. However, other anti-angiogenic drugs, including single targeted TKIs, are currently being evaluated as alternative or salvage therapy after the failure of first-line TKIs. Combinatorial therapy of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling cascade inhibitors has become a highly advocated strategy to improve the low efficiency of the single agent treatment. Recent studies pointed out targetable alternative pathways to overcome the resistance to MAPK and PI3K pathways’ inhibitors. Because radioiodine resistance originates in DTC loss of differentiation, redifferentiation therapies are currently being explored for efficacy. The present review will summarize the conventional management of DTC, the first-line and alternative TKIs in RAIR-DTC, and the approaches that seek to overcome the resistance to MAPK and PI3K pathways’ inhibitors. We also aim to emphasize the latest achievements in the research of redifferentiation therapy, immunotherapy, and agents targeting gene rearrangements in advanced DTC.https://www.mdpi.com/1422-0067/23/7/3470differentiated thyroid cancerradioactive iodine-refractorytargeted therapytyrosine kinase inhibitorPI3K/AKT/mTOR pathwayMAPK pathway |
| spellingShingle | Horatiu Silaghi Vera Lozovanu Carmen Emanuela Georgescu Cristina Pop Bogdana Adriana Nasui Adriana Florinela Cătoi Cristina Alina Silaghi State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer International Journal of Molecular Sciences differentiated thyroid cancer radioactive iodine-refractory targeted therapy tyrosine kinase inhibitor PI3K/AKT/mTOR pathway MAPK pathway |
| title | State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer |
| title_full | State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer |
| title_fullStr | State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer |
| title_full_unstemmed | State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer |
| title_short | State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer |
| title_sort | state of the art in the current management and future directions of targeted therapy for differentiated thyroid cancer |
| topic | differentiated thyroid cancer radioactive iodine-refractory targeted therapy tyrosine kinase inhibitor PI3K/AKT/mTOR pathway MAPK pathway |
| url | https://www.mdpi.com/1422-0067/23/7/3470 |
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